Phenylketonuria: Current Treatments and Future Developments.

Area of Science:

• Biochemistry
• Genetics
• Metabolic Disorders

Background:

• Phenylalanine hydroxylase (PAH) deficiency leads to elevated blood phenylalanine.
• Untreated classical phenylketonuria (PKU) causes severe intellectual disability and adverse fetal effects in pregnancy.
• Therapeutic phenylalanine levels (120-360 µmol/L) are crucial for good patient and fetal outcomes.

Purpose of the Study:

• To review current and emerging treatments for hyperphenylalaninemia.
• To discuss mainstay diet therapy, cofactor therapy, and new enzyme substitution therapy.
• To provide an outlook on novel approaches like microbiome and gene therapy.

Main Methods:

• Review of existing literature on PAH deficiency treatments.
• Analysis of the efficacy of diet therapy, cofactor therapy, and enzyme substitution therapy.
• Exploration of emerging therapeutic strategies.

Main Results:

• Dietary restriction was the sole treatment for decades.
• Cofactor therapy, approved in 2007, is effective in up to 55% of patients, particularly those with milder forms.
• A newly approved enzyme substitution therapy is effective across all patient phenotypes.

Conclusions:

• Hyperphenylalaninemia management has evolved from restrictive diets to targeted therapies.
• Enzyme substitution therapy represents a significant advancement, offering a universal treatment option.
• Future directions include microbiome-based and gene therapies for PAH deficiency.